In the Buck Institute for Age Research’s gleaming $36.5 million stem cell research facility, which opens April 14 in Novato, scientists will seek ways to use stem cells to treat Parkinson’s disease and regenerate cells to restore sight to glaucoma patients.

It is the type of work that many California voters envisioned in 2004 when they approved Proposition 71, the $3 billion bond issue that supported the creation of the California Institute for Regenerative Medicine.

But even as the San Francisco-based stem cell research funding agency nears the halfway point of its life, and the 11th of 12 CIRM-backed major facilities comes on line, the future of the agency itself isn’t quite as clear.

Without stem cell treatments or cures for cancers, diabetes or some other high-profile malady, voters are unlikely to approve a follow-on bond measure, if CIRM seeks one. CIRM leaders haven’t yet settled on how to carry on the agency’s mission after the last of Prop. 71’s funds are turned over to CIRM in five years. Proposals have included a venture philanthropy fund or corporate support that would take potential treatments into mid-stage clinical trials.

CIRM leaders don’t appear to feel under the gun — the agency has time to develop a plan and land a clinical victory to convince voters to approve another bond measure. The last of its funds likely won’t be disbursed to researchers until 2021, said Jon Thomas, chairman of the board that oversees CIRM, and it is setting tight deadlines to move potential therapies from bench to bedside.

“We’re actually a long, long way from running out of money,” Thomas said.

Promises and results

CIRM, whose voter-mandated, 10-year clock didn’t start ticking until it cleared legal challenges in 2007, has awarded more than $1.3 billion. Some $847 million of that total has been paid out for research, training and facilities like the Buck’s new 65,500-square-foot building on its I.M. Pei-planned campus.

Inside the structure, built with a $20.5 million grant from CIRM and a syndicated bank loan, the Buck Institute is moving in about 80 researchers through April. Ultimately, it will house about 125 researchers, said Ralph O’Rear, vice president for facilities at the Buck Institute.

Yet the new building will help the Buck Institute attract more researchers over the next 18 to 24 months. It already has — one of the labs moving into the new facility is run by Henry Jasper, who is moving his research on the role stem cells play in healthy digestion from the University of Rochester in New York state.

Wooing some of the top and soon-to-be top stem cell investigators to California has been one of the benefits of Prop. 71, which made CIRM the world’s deepest-pocketed funder of stem cell research.

What’s more, said Arnold Kriegstein, director of the stem cell program at the University of California, San Francisco, the funding largesse has helped convert traditional medical science researchers into stem cell researchers.

“It really has brought a lot more of our scientists into the realization that some of the things they’re doing can apply and can help patients,” said Kriegstein, whose campus is the third-largest recipient of CIRM grants, at $121 million. “Because of CIRM there are facilities throughout the state recruiting faculty and training researchers.”

To be sure, the Bay Area is a beneficiary of CIRM’s pot of gold. Twenty institutions or companies — from Stanford University to OncoMed Pharmaceuticals Inc. in Redwood City — have raked in close to $470 million in research, training and facilities grants.

But Marcy Darnovsky, associate executive director of the Center for Genetics and Society in Berkeley, said CIRM to date hasn’t done what Prop. 71 promised — find stem cell treatments and cures and ensure that California residents have access to those as affordable products. As a result, she said, it risks hurting science’s standing with the public.

“The campaign made such exaggerated promises. They said the (bond money) would pay for itself, and it’s been nowhere near that,” Darnovsky said. “They promised ‘Cures for California,’ with scientists in white coats going on TV in ad after ad promising that cures were coming and breakthroughs were imminent.”

Darnovsky made similar comments April 10 to an Institute of Medicine panel that is being paid $700,000 by CIRM to evaluate CIRM’s performance. The panel is expected to release its findings in November.

Seeking cures, cash

But CIRM may be turning a corner — at just the right time to secure its future.

Recipients of its 14 “disease team” grants, awarded in 2010 to researchers from multiple California institutions and sometimes from outside the United States, are required to file new drug applications with the Food and Drug Administration in 2014.

Those disease teams are zeroing in on potential treatments for AIDS, stroke, cancers, sickle cell anemia and Lou Gehrig’s disease, among other conditions.

CIRM attached go/no-go milestones to those grants, which ranged from $5.6 million to $20 million. In fact, CIRM withdrew support last month for one of those programs, an effort led by UCSF researcher Mitchel Berger to engineer stem cells to deliver a gene product that is toxic to brain tumors. CIRM had awarded a $19.2 million grant to Berger’s team, but by stopping the project when it did, CIRM saved $13 million, according to an agency report.

“It’s hard to look at all the good, basic science we’ve funded and the translational science and say there’s a cure there,” said Jeff Sheehy, a patient advocate on the CIRM oversight board. “But inevitably there will be a cure there. Biomedical research takes time.”

CIRM is readying a request for proposals for a second set of disease team grants of up to $20 million each that could be awarded later this year.

In the meantime, the agency is looking at different ways to fund its mission after the Prop. 71 cash runs out.

In a state-mandated report earlier this year, Thomas, a lawyer, investment banker and scientist, and CIRM President Alan Trounson outlined alternative funding mechanisms. The options include another bond measure, a venture philanthropy fund to pay for Phase I and Phase II trials of programs, funding from disease foundations that are moving from patient advocacy into basic research funding, federal grants and investment from pharmaceutical companies that could better screen drugs for efficacy and potential safety issues with human stem cells.

CIRM officials, however, are tamping down talk of another state bond.

“We’ve made no decision at this point,” CIRM’s Thomas said.

Whether — and when — CIRM-funded programs pay off in cures is a question to which Kriegstein, for one, doesn’t venture an answer. The earliest applications of stem cells could most likely be as a tool in drug development, such as using the cells to test the toxicity of drugs, rather than the cells becoming a treatment.

“I’ve been amazed at the number of these (programs) moving toward the clinic. Some are destined to fail — that’s the nature of science,” Kriegstein said. “But I am confident that (stem cell research) will be accelerated because of CIRM.”